2ic8



Crystal structure of GlpG

Overview
Escherichia coli GlpG is an integral membrane protein that belongs to the widespread rhomboid protease family. Rhomboid proteases, like site-2 protease (S2P) and gamma-secretase, are unique in that they cleave the transmembrane domain of other membrane proteins. Here we describe the 2.1 A resolution crystal structure of the GlpG core domain. This structure contains six transmembrane segments. Residues previously shown to be involved in catalysis, including a Ser-His dyad, and several water molecules are found at the protein interior at a depth below the membrane surface. This putative active site is accessible by substrate through a large 'V-shaped' opening that faces laterally towards the lipid, but is blocked by a half-submerged loop structure. These observations indicate that, in intramembrane proteolysis, the scission of peptide bonds takes place within the hydrophobic environment of the membrane bilayer. The crystal structure also suggests a gating mechanism for GlpG that controls substrate access to its hydrophilic active site.

A trimer formed in the crystal used for this study, and the authors proposed in their publication that it might be the functional form of the molecule (the Biological Unit). However, senior author Ya Ha said in April 2008 "GlpG probably functions as monomers. We have later solved the structure of a mutant (S201A) of GlpG that crystallized in a different space group.  The trimer observed in the original crystal form was not present in this new structure." (quoted with permission, Eric Martz 00:36, 29 April 2008 (IDT)).

I was unable to visualize the cavity/pocket (journal article Fig. 3c) in Jmol. Eric Martz 06:52, 25 April 2008 (IDT)

About this Structure
2IC8 is a Single protein structure of sequence from Escherichia coli. Full crystallographic information is available from OCA.

Reference
Crystal structure of a rhomboid family intramembrane protease., Wang Y, Zhang Y, Ha Y, Nature. 2006 Nov 9;444(7116):179-80. Epub 2006 Oct 11. PMID:17051161

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